COVID-19 Update: April 21st - May 3rd
Welcome to the McGraw-Hill COVID-19 channel. In this bi-weekly update we have information about the safety of the mRNA vaccines in pregnancy, new treatment guidelines from the NIH and information on the impact of COVID-19 on other chronic illnesses. Finally, we have information on the resumption of the Johnson & Johnson/Janssen vaccine in the United States, a link to the new CDC mask recommendations for those fully vaccinated and a link to the CDC safety guidelines for summer camps.
The NIH has released new guidelines for the treatment of COVID-19. Among the changes are recommendations about use of colchicine, fluvoxamine, monoclonal antibodies, convalescent plasma, and other drugs
Some of the changes include:
- Colchicine: There is insufficient evidence to recommend for or against colchicine in outpatients. The recommendation is against the use of colchicine for inpatients except in the setting of a trial.
- Fluvoxamine: There is insufficient data to recommend for or against fluvoxamine.
- Monoclonal antibodies. Single agent monoclonal antibodies are no longer recommended due to the resistance of several SARS-CoV-2 strains. The combinations of bamlanivimab 700 mg plus etesevimab 1,400 mg or casirivimab 1,200 mg plus imdevimab 1,200 mg are recommended for high risk outpatients (the Emergency Use Authorizations (EUAs) defining “high risk” can be found here for bamlanivimab plus etesevimab and here for casirivimab plus imdevimab).
- Convalescent plasma: Low titer COVID-19 convalescent plasma is no longer authorized for use. Routine use of high titer convalescent plasma is recommended against except in a clinical trial. For those who have impaired immunity, there is insufficient evidence to recommend for or against high-titer convalescent plasma. More information can be found here.
- Tocilizumab is now recommended for use with dexamethasone in some cases. More information can be found here.
- Outpatient treatment of COVID-19. There is a new section on the diagnosis and management of outpatient COVID-19. Outpatient treatment recommendations can be found here.
- Therapeutic Management of Adults with COVID-19. The executive summary including a summary table can be found here.
These recommendations cannot be easily summarized in a couple of paragraphs and should be reviewed by those taking care of inpatients and outpatients with COVID-19. A link to the updated guidelines can be found here.
- NIH COVID-19 Treatment Guidelines: What’s New in the Guidelines Available at https://www.covid19treatmentguidelines.nih.gov/whats-new/ Accessed 21 April 2021.
The mRNA vaccines are safe in pregnancy. In the previous week’s post, we noted that SARS-CoV-2 mRNA vaccines generate a robust antibody response during pregnancy. We now have additional data on the safety of these vaccines during pregnancy. This study looked at vaccine safety registries (v-safe pregnancy registry, Vaccine Adverse Event Reporting System (VAERS)) to determine the safety of mRNA vaccines during pregnancy1. 35,691 pregnant individuals were identified between the ages of 16-54.
Injection site reactions were identified more frequently in pregnant patients whereas most systemic reactions, except for nausea and vomiting, were reported more frequently in non-pregnant patients.
3958 v-safe patients were followed up by phone of whom 827 had a completed pregnancy. Rates of spontaneous abortion (<20 weeks), stillbirth ≥ 20 weeks, preterm birth, congenital anomalies, etc. were comparable to the baselines published in the literature (although the groups were not matched for age, “race”, ethnicity, etc.).
This study is reassuring. The rate of adverse pregnancy outcomes after SARS-CoV-2 mRNA vaccination is comparable to baseline rates. Given the known adverse impact of COVID-19 on pregnancy, we should encourage vaccination.
- Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons DOI: 10.1056/NEJMoa2104983 https://www.nejm.org/doi/full/10.1056/NEJMoa2104983 accessed 1 May 2021
- Villar J, Ariff S, Gunier RB, et al. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr. Published online April 22, 2021. doi:10.1001/jamapediatrics.2021.1050
COVID-19 may have adverse effects on chronic health conditions. Post-acute COVID-19 syndrome (PACS/”Long hauler syndrome”) is well described: fatigue, “brain fog”, respiratory complaints, myalgias, anosmia, etc. This study looks at the effects of COVID-19 infection on long-term mortality and chronic illnesses such a cardiac disease and diabetes, etc. This is a cohort study of 73,435 patients in the Veteran’s Health Administration (VA) who were at least 30 days out after a COVID-19 diagnosis. None of the patients had been hospitalized. They looked at the risk of death at 30 days and 6 months, the risk of cardiovascular conditions, metabolic disorders and more. The control group included 5,000,000 unhospitalized VA patients who were never diagnosed with COVID-19.
The hazard ratio for death greater than 30 days from the diagnosis of COVID-19 was HR 1.59 (95%CI 1.46-1.73). At 6 months, excess deaths were estimated to be 8.39 per 1000. (95%CI 7.09-9.58). Heart failure, dysrhythmias, the use of hypoglycemic agents, the use of opioids, esophageal disorders and more were also noted to be increased. The full study can be found here.
The excess deaths are concerning. The other associations are at least somewhat suspect. They looked at 379 diagnoses, 380 medication classes, and 62 lab abnormalities. One would expect several positive associations by chance alone. Additionally, association doesn’t mean causality. Patients with a history of COVID-19 may have been seen more frequently leading to a higher rate of diagnosis and medication prescribing. Finally, we can’t be sure that any of the diagnoses are a result of COVID-19. That said, we should take the opportunity to take a good history and do age-appropriate screening in patients we are following up after COVID19.
- Al-Aly, Z., Xie, Y. & Bowe, B. High-dimensional characterization of post-acute sequalae of COVID-19. Nature (2021). https://doi.org/10.1038/s41586-021-03553-9
The Johnson & Johnson/Janssen vaccine has been cleared for use in the United States after a temporary pause secondary to a concern about thrombosis with thrombocytopenia. The Advisory Committee on Immunization Practices (ACIP) concluded that the benefit of the of the Johnson & Johnson/Janssen COVID-19 vaccine outweighs the risk vis-à-vis thrombosis with thrombocytopenia. These cases were seen primarily in women 18-49 years of age and a warning has been added to the Emergency Use Authorization (EUA).
To put this in perspective, the BMJ notes that an unpublished study from the University of Oxford suggests that cerebral venous thrombosis occurs in 39 per million cases of COVID-19 compared to 4 per million in those receiving the Johnson & Johnson/Janssen vaccine (RR 6.36, p<0.001). The EUA and information for patients and providers can be found here.
- MacNeil JR, Su JR, Broder KR, et al. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021. MMWR Morb Mortal Wkly Rep 2021;70:651-656. DOI: http://dx.doi.org/10.15585/mmwr.mm7017e4
- Covid-19: Risk of cerebral blood clots from disease is 10 times that from vaccination, study finds. BMJ 2021; 373 doi: https://doi.org/10.1136/bmj.n1005 (Published 16 April 2021)
- U.S. FDA. Janssen COVID-19 Vaccine. Updated April 23, 2021. Available at https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/Janssen-covid-19-vaccine
There are new CDC recommendations for outdoor mask use in those who are fully vaccinated and who are not immunocompromised. Among the points (verbatim):
- Immunocompromised individuals need to consult their healthcare provider about these recommendations, even if fully vaccinated.
- Fully vaccinated people no longer need to wear a mask outdoors, except in certain crowded settings and venues.
- Fully vaccinated workers no longer need to be restricted from work following an exposure as long as they are asymptomatic.
- Fully vaccinated residents of non-healthcare congregate settings no longer need to quarantine following a known exposure.
- Fully vaccinated people can visit with other fully vaccinated people indoors without wearing masks or physical distancing.
- CDC: COVIC-19. Interim Public Health Recommendations for Fully Vaccinated People. Updated, April 29th Available at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated-guidance.html
Finally, the CDC has released new guidelines for safe interactions at summer camps. Those working in such settings should review these recommendations. They can be found here.
- CDC: COVID-19. Guidance for Operating Youth and Summer camps During COVID-19. Updated 24 April 2021. Available at https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/summer-camps.html